Structure of PDB 6dr0 Chain A Binding Site BS02

Receptor Information

>6dr0 Chain A (length=2188) Species: 9606 (Homo sapiens)

SSFLHIGDIVSLYAEGSVNGFISTLGLVDDRCVVEPAAGDLDNPPKKFRD
CLFKVCPMNRYSAQKQYWKAKQDVVLLQKLQHAAQMEQKQNDTENKKVHG
DVVKYGSVIQLLHMKSNKYLTVNKRLPALLEKNAMRVTLDATGNEGSWLF
IQPFWKLRSNGDNVVVGDKVILNPVNAGQPLHASNYELSDNAGCKEVNSV
NCNTSWKINLFMQFRDHLEEVLKGGDVVRLFHAEQEKFLTCDEYKGKLQV
FLRTTLRQSATSATSSNALWEVEVVHHDPCRGGAGHWNGLYRFKHLATGN
YLAAEENPSYKYCLVAVPHGNDIASLFELDPTTLQKTDSFVPRNSYVRLR
HLCTNTWIQSTNVPIDIEEERPIRLMLGTCPTKEDKEAFAIVSVPVSEIR
DLDFANDASSMLASAVEKLNEGFISQNDRRFVIQLLEDLVFFVSDVPNNG
QNVLDIMVTKPNRERQKLMREQNILKQVFGILKAPFRPLVRLEELSDQKN
APYQHMFRLCYRVLRHSQEDYRKNQEHIAKQFGMMQSQIGYDILAEDTIT
ALLHNNRKLLEKHITKTEVETFVSLVRKNREPRFLDYLSDLCVSNHIAIP
VTQELICKCVLDPKNSDILIRTELRPEEVWLTWTDKNNEHHEKSVRQLAQ
EARAGNAHDENVLSYYRYQLKLFARMCLDRQYLAIDEISQQLGVDLIFLC
MADEMLPFDLRASFCHLMLHVHVDRDPQELVTPVKFARLWTEIPTAITIK
DYDSNLNASRDDKKNKFANTMEFVEDYLNNVVSEAVPFANEEKNKLTFEV
VSLAHNLIYFGFYSFSELLRLTRTLLGIIDDIVVMETKLKILEILQFILN
VRLDYRISYLLSVFKKEFVEVFPNLDRIGEQAEAMFGSMLEVDDEGGRMF
LRVLIHLTMHDYAPLVSGALQLLFKHFSQRQEAMHTFKQVQLLISAQDVE
NYKVIKSELDRLRTMVEKSELWVDSENYQIVKGILERLNKMCGVGEQMRK
KQQRLLKNMDAHKVMLDLLQIPYDKGDAKMMEILRYTHQFLQKFCAGNPG
NQALLHKHLHLFLTPGLLEAETMQHIFLNNYQLCSEISEPVLQHFVHLLA
THGRHVQYLDFLHTVIKAEGKYVKKCQDMIMTELTNAGDDVVVFYNDKAS
LAHLLDMMKAARDGVEDHSPLMYHISLVDLLAACAEGKNVYTEIKCTSLL
PLEDVVSVVTHEDCITEVKMAYVNFVNHCYVDTEVEMKEIYTSNHIWTLF
ENFTLDMARVCSKRTLEKYVLSVVLDTINAFFSSPAMVAKGRAILLPMDL
DAHIASCAAAAQRNASSYKATTRAFPRVTPTANQWDYKNIIEKLQDIITA
LEERLKPLVQAELSVLVDVLHWPELLFLEGSEAYQRCESGGFLSKLIQHT
KDLMESEEKLCIKVLRTLQQMLLKKTKYGDRGNQLRKMLLQNYLQWSAIA
ATQCRLDKEGATKLVCDLITSTKNEKIFQESIGLAIHLLDGGNTEIQKSF
HNLMMSDKKSERFFKVLHDRMKRAQQETKSTVMGTSVLIMQPILRFLQLL
CENHNRDLQNFLRCQNNKTNYNLVCETLQFLDIMCGSTTGGLGLLGLYIN
EDNVGLVIQTLETLTEYCQGPCHENQTCIVTHESNGIDIITALILNDISP
LCKYRMDLVLQLKDNASKLLLALMESRHDSENAERILISLRPQELVDVIK
KAYLQEEERENSEVSPREVGHNIYILALQLSRHNKQLQHLLKPVEDPLAY
YENHTSQIEIVRQDRSMEQIVFPVPGICQFLTEETKHRLFTTTEQDEQGS
KVSDFFDQSSFLHNEMEWQRKLRSMPLIYWFSRRMTLWGSISFNLAVFIN
IIIAFFYPYLISLLFWILICFSIAALFTKRYSIRPLIVALILRSIYYLGI
GPTLNILGALNLTNKIVFVVSFVGNRGTFIRGYKAMVMDMEFLYHVGYIL
TSVLGLFAHELFYSILLFDLIYREETLFNVIKSVTRNGRSILLTALLALI
LVYLFSIVGFLFLKDDFILEVDRLPDSTERACDTLLMCIVTVMNHGLRNG
GGVGDILRKPSKDESLFPARVVYDLLFFFIVIIIVLNLIFGVIIDTFADL
RSEKQKKEEILKTTCFICGLERDKFDNKTVSFEEHIKLEHNMWNYLYFIV
LVRVKNKTDYTGPESYVAQMIKNKNLDWFPRMRAMSLV

Ligand information

• Ligand ID: I3P
• InChI: InChI=1S/C6H15O15P3/c7-1-2(8)5(20-23(13,14)15)6(21-24(16,17)18)3(9)4(1)19-22(10,11)12/h1-9H,(H2,10,11,12)(H2,13,14,15)(H2,16,17,18)/t1-,2+,3+,4-,5-,6-/m1/s1
• InChIKey: MMWCIQZXVOZEGG-XJTPDSDZSA-N
• SMILES:
  ACDLabs 10.04: O=P(OC1C(O)C(O)C(OP(=O)(O)O)C(O)C1OP(=O)(O)O)(O)O
  OpenEye OEToolkits 1.5.0: C1(C(C(C(C(C1OP(=O)(O)O)O)OP(=O)(O)O)OP(=O)(O)O)O)O
  CACTVS 3.341: O[CH]1[CH](O)[CH](O[P](O)(O)=O)[CH](O[P](O)(O)=O)[CH](O)[CH]1O[P](O)(O)=O
  OpenEye OEToolkits 1.5.0: [C@H]1([C@@H]([C@H]([C@@H]([C@H]([C@@H]1OP(=O)(O)O)O)OP(=O)(O)O)OP(=O)(O)O)O)O
  CACTVS 3.341: O[C@@H]1[C@H](O)[C@@H](O[P](O)(O)=O)[C@H](O[P](O)(O)=O)[C@@H](O)[C@@H]1O[P](O)(O)=O
• Formula: C6 H15 O15 P3
• Name: D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE
• ChEMBL: CHEMBL279107
• DrugBank: DB03401
• ZINC: ZINC000004095598
• PDB chain: 6dr0 Chain A Residue 2702

Receptor-Ligand Complex Structure

Structure summary

• PDB: 6dr0 Structural basis for the regulation of inositol trisphosphate receptors by Ca2+and IP3.
• Resolution: 4.47 Å
• Binding residue (original residue number in PDB): R266 T268 K507 R568 K569
• Binding residue (residue number reindexed from 1): R253 T255 K467 R522 K523
• Annotation score: 1
• Binding affinity: BindingDB: Kd=195nM

Gene Ontology

Molecular Function

• GO:0000822 inositol hexakisphosphate binding
• GO:0005216 monoatomic ion channel activity
• GO:0005220 inositol 1,4,5-trisphosphate-gated calcium channel activity
• GO:0005262 calcium channel activity
• GO:0005509 calcium ion binding
• GO:0005515 protein binding
• GO:0015278 intracellularly gated calcium channel activity
• GO:0035091 phosphatidylinositol binding
• GO:0043533 inositol 1,3,4,5 tetrakisphosphate binding
• GO:0070679 inositol 1,4,5 trisphosphate binding

Biological Process

• GO:0006811 monoatomic ion transport
• GO:0006816 calcium ion transport
• GO:0007186 G protein-coupled receptor signaling pathway
• GO:0007204 positive regulation of cytosolic calcium ion concentration
• GO:0007613 memory
• GO:0019722 calcium-mediated signaling
• GO:0030168 platelet activation
• GO:0050909 sensory perception of taste
• GO:0050913 sensory perception of bitter taste
• GO:0050916 sensory perception of sweet taste
• GO:0050917 sensory perception of umami taste
• GO:0051209 release of sequestered calcium ion into cytosol
• GO:0051289 protein homotetramerization
• GO:0051592 response to calcium ion
• GO:0055074 calcium ion homeostasis
• GO:0055085 transmembrane transport
• GO:0060291 long-term synaptic potentiation
• GO:0070588 calcium ion transmembrane transport

Cellular Component

• GO:0005634 nucleus
• GO:0005640 nuclear outer membrane
• GO:0005654 nucleoplasm
• GO:0005730 nucleolus
• GO:0005737 cytoplasm
• GO:0005783 endoplasmic reticulum
• GO:0005789 endoplasmic reticulum membrane
• GO:0005886 plasma membrane
• GO:0005903 brush border
• GO:0016020 membrane
• GO:0016529 sarcoplasmic reticulum
• GO:0030658 transport vesicle membrane
• GO:0030667 secretory granule membrane
• GO:0031095 platelet dense tubular network membrane
• GO:0031410 cytoplasmic vesicle
• GO:0043025 neuronal cell body
• GO:0043235 receptor complex
• GO:0045177 apical part of cell
• GO:0098554 cytoplasmic side of endoplasmic reticulum membrane

External links

• PDB: RCSB:6dr0, PDBe:6dr0, PDBj:6dr0
• PDBsum: 6dr0
• PubMed: 30013099
• UniProt: Q14573|ITPR3_HUMAN Inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 (Gene Name=ITPR3)